How do different opioids compare in strength to morphine. What factors influence opioid potency beyond just dosage. Which opioids are considered the strongest and weakest. How can understanding opioid equivalence help prevent overdose.

Understanding Opioid Potency and Equivalence

Opioids are a class of drugs that include both prescription pain medications and illicit substances like heroin. While all opioids work by binding to opioid receptors in the brain and body, their potency can vary significantly. Understanding opioid potency and equivalence is crucial for proper dosing, pain management, and preventing overdose.

The potency of an opioid refers to how strong its effects are relative to a standard dose. Morphine is often used as the reference point, with other opioids described in terms of their potency relative to morphine. For example, hydromorphone is considered about 5 times more potent than morphine, while codeine is about 1/10 as potent.

However, potency alone doesn’t tell the full story. Other factors that influence an opioid’s overall strength and effects include:

• Bioavailability – how much of the drug reaches circulation when administered
• Half-life – how long the drug remains active in the body
• Formulation – immediate vs. extended-release
• Route of administration – oral, intravenous, transdermal, etc.
• Individual patient factors – tolerance, metabolism, etc.

Understanding these nuances is essential for healthcare providers when prescribing opioids and for patients to use them safely. Let’s explore opioid potency in more detail.

Opioid Equivalence Chart: Comparing Potency to Morphine

The World Health Organization (WHO) provides a helpful chart comparing the potency of various opioids to morphine. This allows for easier conversion between different opioids when changing medications or doses. Here is a summary of the WHO opioid equivalence data:

Using this chart, we can see that 1 mg of oral hydromorphone is approximately equivalent to 5 mg of oral morphine in terms of analgesic effect. However, it’s crucial to note that these are approximate equivalences and individual responses may vary.

The Strongest Opioids: Potent Pain Relievers and Their Risks

While all opioids can be dangerous if misused, some are particularly potent and carry a higher risk of overdose. Which opioids are considered the strongest?

• Fentanyl: 50-100 times more potent than morphine
• Carfentanil: 10,000 times more potent than morphine
• Sufentanil: 5-10 times more potent than fentanyl
• Remifentanil: Similar potency to fentanyl, but shorter-acting

These ultra-potent synthetic opioids are typically only used in medical settings for severe pain or anesthesia. However, illicit versions have become increasingly common in the street drug supply, contributing to the opioid overdose crisis.

The extreme potency of these drugs means that even tiny amounts can be fatal. For example, just 2 milligrams of fentanyl (about the size of a few grains of salt) can be lethal to an opioid-naive person. This makes proper dosing absolutely critical and increases overdose risk, especially when these drugs are mixed into other substances without the user’s knowledge.

Weaker Opioids: Lower Potency Options for Pain Management

On the other end of the spectrum, some opioids are considered relatively weak compared to morphine. These include:

• Codeine: About 1/10 as potent as morphine
• Tramadol: About 1/10 as potent as morphine
• Dextropropoxyphene: About 1/2 as potent as codeine

These weaker opioids are often used for mild to moderate pain or as a step down from stronger opioids. They may be combined with non-opioid pain relievers like acetaminophen for added effect. While they carry a lower risk of overdose compared to more potent opioids, they can still be addictive and cause side effects, especially at higher doses.

It’s important to note that even these “weaker” opioids can be dangerous if misused or combined with other central nervous system depressants like alcohol or benzodiazepines. No opioid should be considered completely safe or non-addictive.

Factors Influencing Opioid Potency Beyond Dosage

While the equivalence chart provides a good starting point for comparing opioid potency, several other factors can influence how strong an opioid’s effects are in practice:

Route of Administration

The way an opioid is taken can significantly affect its potency and onset of action. Generally, the potency hierarchy from strongest to weakest is:

1. Intravenous (IV)
2. Intramuscular (IM) or subcutaneous (SC)
3. Intranasal
4. Transmucosal (buccal/sublingual)
5. Transdermal
6. Oral

For example, IV morphine is about 3 times more potent than oral morphine due to higher bioavailability and faster onset.

Formulation

Immediate-release formulations typically have a faster onset and higher peak effect, while extended-release formulations provide longer-lasting pain relief but may have lower peak concentrations. This can affect perceived potency and risk of overdose.

Individual Factors

Patient-specific factors like age, weight, metabolism, liver/kidney function, and opioid tolerance can all influence how strongly an individual responds to a given opioid dose. This is why careful titration and personalized dosing are essential in pain management.

Using Opioid Equivalence to Prevent Overdose

Understanding opioid potency and equivalence is crucial for preventing accidental overdose, especially when switching between different opioids or formulations. How can this knowledge be applied to improve safety?

• When changing from one opioid to another, use equivalence charts to calculate an appropriate starting dose
• Always start with a lower equivalent dose (usually 25-50% less) when switching opioids due to incomplete cross-tolerance
• Be aware that some opioids (like methadone) have complex pharmacokinetics that make simple conversions unreliable
• Consider individual patient factors and consult with pain management specialists for complex cases
• Educate patients about the relative strength of different opioids to prevent accidental overdose

Healthcare providers should also be aware of the limitations of equivalence charts. These provide general guidelines but may not account for all factors affecting an individual’s response to opioids. Clinical judgment and careful monitoring are always necessary when prescribing or changing opioid medications.

Special Considerations for Methadone and Buprenorphine

Two opioids that require special consideration when discussing potency and equivalence are methadone and buprenorphine. Both are used not only for pain management but also for opioid addiction treatment, and they have unique properties that set them apart from other opioids.

Methadone

Methadone is notoriously difficult to convert to other opioids due to its complex pharmacokinetics. While a single 5 mg dose of methadone may be equivalent to about 7.5 mg of morphine, with regular administration its relative potency increases dramatically. This is due to methadone’s long and variable half-life, as well as its activity at multiple receptor types.

The WHO chart gives a wide range of 4-12 times the potency of morphine for methadone, but in practice, it can be even higher for patients on long-term methadone therapy. This makes switching from methadone to other opioids particularly dangerous and requires careful, gradual titration under close medical supervision.

Buprenorphine

Buprenorphine is a partial opioid agonist with a unique pharmacological profile. It has a very high affinity for opioid receptors but only partial activation, creating a “ceiling effect” on respiratory depression. This makes it safer in terms of overdose risk compared to full agonist opioids.

However, buprenorphine’s high receptor affinity can complicate switching to or from other opioids. It can block the effects of other opioids and potentially precipitate withdrawal in opioid-dependent individuals. The WHO chart gives a potency range of 75-115 times that of morphine for sublingual buprenorphine, but conversions should be done cautiously and under medical supervision.

The Role of Non-Opioid Factors in Pain Management

While understanding opioid potency is crucial for safe and effective pain management, it’s important to remember that opioids are just one tool in the pain management toolbox. A comprehensive approach to pain should consider:

• Non-opioid medications (e.g., NSAIDs, acetaminophen, gabapentinoids)
• Topical treatments
• Physical therapy and exercise
• Psychological interventions (e.g., cognitive-behavioral therapy)
• Complementary therapies (e.g., acupuncture, massage)
• Interventional procedures (e.g., nerve blocks)

In many cases, a multimodal approach combining several of these strategies can provide better pain relief with lower opioid doses, reducing the risk of side effects and addiction. Healthcare providers should consider the full range of pain management options and tailor treatment to each patient’s individual needs and circumstances.

Understanding opioid potency and equivalence is just one piece of the puzzle in effective pain management. By combining this knowledge with a comprehensive, patient-centered approach, healthcare providers can optimize pain relief while minimizing risks associated with opioid use.

Table A6.2, Approximate potency of opioids relative to morphine; PO and immediate-release formulations unless stated otherwisea – WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. Geneva: World Health Organization; 2018.

WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents.

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Table A6.2Approximate potency of opioids relative to morphine; PO and immediate-release formulations unless stated otherwise

^a

Source: Adapted with permission from Twycross et al. 2017:371 (Table 4) (3).

a

Multiply dose of opioid in the first column by relative potency in the second column to determine the equivalent dose of morphine sulfate/hydrochloride; conversely, divide morphine dose by the relative potency to determine the equivalent dose of another opioid.

b

Dependent in part on severity of pain and on dose; often longer-lasting in very elderly and those with renal impairment.

c

The numbers in parenthesis are the manufacturers’ preferred relative potencies.

d

A single 5 mg dose of methadone is equivalent to morphine 7.5 mg, but a variable long plasma half-life and broad-spectrum receptor affinity result in a much higher-than-expected relative potency when administered regularly – sometimes much higher than the range given above. Therefore, guidance from a specialist is recommended for conversions to regularly administered methadone.

From: ANNEX 6, Pharmacological Profiles and Opioid Conversion Tables

© World Health Organization 2018.

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Discover the List of Opioids From Strongest to Weakest to Avoid Overdose Updated 2023

September 11, 2017
by Mark Adams

A Guide to Addictive Opiates: List of Opioids Strongest to Weakest

Post updated 3-10-2023

Creating a list of opioids from strongest to weakest is not as straightforward as simply listing them by potency or by an analgesic effect. A report released by the CDC (1) listed various narcotic pain medications by strength as they compared to morphine. Yet the list doesn’t determine whether the medication also has a similar mechanism of action. Some of the strongest types of pain medication in a hospital may have a similar potency to morphine, but they may also be formulated with a dose ceiling, while morphine does not, rendering them less potent overall.  

The actual potency of some narcotic pain medications and prescription opioids, or pain relievers by strength, may also vary, depending on the route of administration.  Essentially, the list of opioids strongest to weakest is determined by factoring in that a smaller dose of certain painkiller medications may be required to achieve the same pain-relief response to treat severe pain as can be reached with morphine.

With those determinations in mind, the list of common opioids from strongest to weakest is also broken down into three classifications: stronger than morphine, morphine-equivalent and weaker than morphine.

Stronger than Morphine

Opioid use disorders (OUD) are on the rise. Let’s take a look at some of the drugs that are stronger than morphine.

Fentanyl (Duragesic)

 Fentanyl is common among drug abusers and is one of the strongest opioids on the market and is the strongest pain medication in hospital settings. This drug can lead to abuse and addiction. The opioid painkiller medication has a rapid onset and short duration of action. It’s occasionally used as a part of the anesthesia process to help prevent pain following surgery but it is also used to treat severe pain. Depending on the method of administration, it’s estimated that fentanyl can be up to 100 times more potent than morphine and is classified as one of the strongest opioids.

Oxymorphone (Opana ER, Numorphan)

Oxymorphone is a semi-synthetic opioid painkiller medication commonly used to treat severe to chronic pain and to maintain anesthesia. The powerful opioid medication is highly addictive and requires an opioid addiction treatment program to overcome, leading the FDA to ask the manufacturer to remove it from the US market in 2017.

Hydromorphone (Dilaudid, Exalgo, Contin)

Hydromorphone is synthesized from morphine and is commonly used in hospital settings to treat moderate to severe pain. The medication is more soluble in water than morphine, which allows the drug to be delivered in a smaller amount of water.

Heroin (diamorphine)

Heroin is created by combining the morphine alkaloid with acetic anhydride to create a more potent opioid analgesic drug. While heroin was once used in medical settings, it was made a Schedule I Substance under the Controlled Substances Act in 1924 and is now an illicit drug used primarily for recreational purposes. It’s estimated that heroin is approximately 2 to 4 times more potent than morphine. Heroin addiction is a contributing factor to the drug epidemic that the U.S. is facing and is leading to mass overdose deaths. 

Levorphanol (Levo-Dromoran)

Levorphanol is a synthetic opioid painkiller medication created from the compound racemorphan and used to treat moderate to severe pain. Levorphanol is produced using one of the two enantiomers of the compound racemorphan. Levorphanol is several times more potent than morphine and is strongly addicting.

Methadone (Dolophine, Methadone)

Methadone is an opioid painkiller medication used to treat moderate to severe pain. It’s also prescribed to treat opioid dependence in methadone maintenance programs.  It is considered more potent than morphine due to its effectiveness against neuropathic pain. There is also a lower risk of the user developing dose tolerance with methadone (2) as compared to other types of opioids.

Oxycodone (OxyContin, Roxicodone)

Oxycodone has a greater analgesic effect than morphine (6). The semi-synthetic opioid is synthesized from thebaine, an alkaloid found in the opium poppy and is approximately 1.5 times stronger than morphine.

Morphine-Equivalent

Tapentadol (Nucynta, Palexia SR): Technically, tapentadol could be classified as stronger than morphine, as clinical trials (3) indicate the medication provides superior analgesic effects than equivalent doses of oxycodone, but with significantly lower gastrointestinal side effects. However, as tapentadol has a dose ceiling, so it’s listed as a morphine-equivalent ahead in order of strength to morphine.

Morphine (Astramorph, Avinza, Kadian)

Morphine is created from the morphine alkaloid found within the opium poppy and is commonly used to treat moderate to severe pain. Approximately 70% of morphine produced is used as a base to create other opioid medications (5), including oxymorphone, hydromorphone, and heroin.

Hydrocodone (Zohydro ER)

Hydrocodone is a semi-synthetic opiate analgesic created from the codeine alkaloid found within the opium poppy.  Hydrocodone is commonly used to treat moderate to severe pain and is predominantly used within the United States, with 99% of the world’s volume of hydrocodone consumed in that country. Hydrocodone is also commonly available in a variety of formulations, including combinations with paracetamol (Vicodin), ibuprofen (Vicoprofen), or aspirin (Lortab).

Weaker Than Morphine

Pethidine (Meperidine, Demerol)

Pethidine is a synthetic opioid painkiller medication and is usually prescribed to treat moderate to severe pain. While it provides almost equivalent levels of pain relief to morphine in treating post-surgical pain, the method of administration may differ and the dosage used may need to be slightly higher than the comparative dose of morphine to achieve similar results (4).

Codeine

Codeine is created from the codeine alkaloid found within the opium poppy that is commonly used to treat mild to moderate pain. Codeine’s efficacy comes from the drug being broken down in the liver into morphine. Codeine is the most commonly taken opiate medication in the world (5).

Tramadol (Ultram)

Tramadol is an opiate painkiller medication used to treat moderate pain. The medication is synthesized as a racemic mixture using both components of R- and S-stereoisomers.

Laudanum (Opium Tincture)

Of the list of opioids strongest to weakest, the least potent opiate is still available from some pharmacies in the US and UK. The formulation is used primarily to control diarrhea or to ease withdrawal symptoms in babies born to opiate-addicted mothers. In the 1800s morphine was known as laudanum and was readily available from grocers and markets, but was soon restricted once its addictive qualities were known. Today, laudanum is sold as a ‘tincture of opium,’ which contains approximately 10% (100mg) powdered opium, or the equivalent of 1% (10mg) morphine per milliliter. The tincture is considered a single formulation, as it contains all of the alkaloids found within the opium poppy.

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